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Assessing the Intricate Balance of Intermolecular Interactions upon Self-Association of Intrinsically Disordered Proteins

Rieloff, Ellen LU ; Tully, Mark D. and Skepö, Marie LU (2019) In Journal of Molecular Biology 431(3). p.511-523
Abstract

Attractive interactions between intrinsically disordered proteins can be crucial for the functionality or, on the contrary, lead to the formation of harmful aggregates. For obtaining a molecular understanding of intrinsically disordered proteins and their interactions, computer simulations have proven to be a valuable complement to experiments. In this study, we present a coarse-grained model and its applications to a system dominated by attractive interactions, namely, the self-association of the saliva protein Statherin. SAXS experiments show that Statherin self-associates with increased protein concentration, and that both an increased temperature and a lower ionic strength decrease the size of the formed complexes. The model... (More)

Attractive interactions between intrinsically disordered proteins can be crucial for the functionality or, on the contrary, lead to the formation of harmful aggregates. For obtaining a molecular understanding of intrinsically disordered proteins and their interactions, computer simulations have proven to be a valuable complement to experiments. In this study, we present a coarse-grained model and its applications to a system dominated by attractive interactions, namely, the self-association of the saliva protein Statherin. SAXS experiments show that Statherin self-associates with increased protein concentration, and that both an increased temperature and a lower ionic strength decrease the size of the formed complexes. The model captures the observed trends and provides insight into the size distribution. Hydrophobic interaction is considered to be the major driving force of the self-association, while electrostatic repulsion represses the growth. In addition, the model suggests that the decrease of association number with increased temperature is of entropic origin.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
coarse-graining, intrinsically disordered proteins, Monte Carlo simulations, SAXS, self-association
in
Journal of Molecular Biology
volume
431
issue
3
pages
511 - 523
publisher
Elsevier
external identifiers
  • scopus:85058374244
  • pmid:30529747
ISSN
0022-2836
DOI
10.1016/j.jmb.2018.11.027
language
English
LU publication?
yes
id
4a675b53-0c78-4eb6-bfb6-4d671f2665fd
date added to LUP
2019-01-08 14:19:39
date last changed
2020-03-24 06:35:19
@article{4a675b53-0c78-4eb6-bfb6-4d671f2665fd,
  abstract     = {<p>Attractive interactions between intrinsically disordered proteins can be crucial for the functionality or, on the contrary, lead to the formation of harmful aggregates. For obtaining a molecular understanding of intrinsically disordered proteins and their interactions, computer simulations have proven to be a valuable complement to experiments. In this study, we present a coarse-grained model and its applications to a system dominated by attractive interactions, namely, the self-association of the saliva protein Statherin. SAXS experiments show that Statherin self-associates with increased protein concentration, and that both an increased temperature and a lower ionic strength decrease the size of the formed complexes. The model captures the observed trends and provides insight into the size distribution. Hydrophobic interaction is considered to be the major driving force of the self-association, while electrostatic repulsion represses the growth. In addition, the model suggests that the decrease of association number with increased temperature is of entropic origin.</p>},
  author       = {Rieloff, Ellen and Tully, Mark D. and Skepö, Marie},
  issn         = {0022-2836},
  language     = {eng},
  number       = {3},
  pages        = {511--523},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Assessing the Intricate Balance of Intermolecular Interactions upon Self-Association of Intrinsically Disordered Proteins},
  url          = {http://dx.doi.org/10.1016/j.jmb.2018.11.027},
  doi          = {10.1016/j.jmb.2018.11.027},
  volume       = {431},
  year         = {2019},
}